Description

Summary

T cells, a type of white blood cell called a lymphocyte, play an important role in the immune system. One subtype, the regulatory T cell (Treg) helps to regulate the immune system and may provide protection against the development of autoimmune disease. The hope is that these naturally occurring Treg cells can be utilized for the treatment of autoimmune disease and potentially replace the use of chronic immunosuppressive therapies that are associated with multiple side effects. There has been a small study showing safe administration of Tregs with decreased disease activity in patients with insulin-dependent diabetes. Tregs are being studied in lupus, cancer and organ transplantation. This phase I trial will be conducted as an open-label, dose-escalation, multicenter trial in adult participants with active pemphigus.The purpose of this study is to test the safety and effect of Treg therapy in participants who have skin (cutaneous) involvement due to pemphigus.

Official Title

Details

Up to 12 adults between the ages of 18 and 75 years of age who have been diagnosed with pemphigus and meet all other entry criteria will be enrolled to receive one infusion of their own expanded Tregs at one of the following doses:

2.5 x 108 PolyTregs or

10 x 108 PolyTregs.

Safety, disease activity, and mechanism of action will be assessed over a three year period, using biospecimens from blood and skin. Study therapy administration will occur during an overnight stay, followed by 2 weekly visits, then monthly visits from Week 8 to Week 12, then quarterly visits from Week 26 to Week 52, then twice a year visits until Week 156.

Keywords

Eligibility

You can join if…

Open to people ages 18–75

Ability to provide informed consent;

Diagnosis of Pemphigus Vulgaris (PV) or Pemphigus Foliaceus (PF), defined by H&E staining (e.g., Haemotoxylin and Eosin) and direct immunofluorescence staining of skin biopsy at any time prior to enrollment;

Pemphigus treated with systemic corticosteroids within the 2 years prior to screening(historic or current);

You CAN'T join if...

Addition of a new medication, or change in the dose of any background medication used to treat any aspect of pemphigus within the timeframes listed below. Specifically:

methotrexate, mycophenolate mofetil, mycophenolic acid, azathioprine,cyclosporine or dapsone within the 6 weeks prior to screening or in the time between screening and study drug infusion,

intravenous Immunoglobulin (IVIG) within 12 weeks prior to screening or in the time between screening and study drug infusion (subjects on IVIG must be on stable dose for at least 12 weeks prior to screening),

treatment with cyclophosphamide within 12 weeks prior to screening or in the time between screening and study drug infusion.

an indeterminate QuantiFERON (R)-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation with and clearance by local infectious disease (ID) department.

Chronic infection that is currently being treated with suppressive anti-infective therapy, including but not limited to tuberculosis, pneumocystis, CMV, herpes zoster,and atypical mycobacteria, with the exception of historical orolabial or localized cutaneous herpes simplex infections treated with suppressive anti- viral therapy;

Receipt of a live-attenuated vaccine within 12 months prior to screening;

Concomitant malignancies or a history of malignancy, with the exception of completely treated basal cell carcinoma of the skin;

Pregnancy;

Lactating or breastfeeding;

Unwilling or unable to use reliable method(s) of contraception:

For females of child-bearing potential, from four weeks prior to Day 0 through

1 year after Treg dosing;

For males, from the day of Treg infusion (baseline visit) to three months after Treg infusion.

Use of an investigational therapeutic medication, or other biologic medications except rituximab, within the past 90 days, or 5 half-lives prior to screening, whichever is greater;

Concomitant medical condition that places the subject at risk by participating in this study, including but not limited to: